Breast Cancer Drug Therapy Findings Alter Standard of Care

By: Carrie Frye
Thursday, April 23, 2015

A breakthrough in research on human epidermal growth factor receptor 2 (HER2) positive breast cancer used a three-drug combination to produce median survivorship of more than four years.

A randomized study group with HER2-positive metastatic breast cancer who received pertuzumab, trastuzumab and docetaxel as a targeted therapy achieved a median survival rate of 56.5 months — 15.7 months longer than the rate achieved among those who received docetaxel, trastuzumab and a placebo. The study, published in The New England Journal of Medicine in February, is based upon clinical research by the authors tracking patient outcomes as part of the CLEOPATRA Study Group since 2008. A major development in breast cancer research, the findings have changed the standard-of-care treatment for HER2-positive breast cancer.

“This is a great success story with HER2,” says Sandra M. Swain, MD, FACP, FASCO, Director of the Washington Cancer Institute at MedStar Washington Hospital Center in Washington and co-principal investigator for CLEOPATRA. “With these results, I am extremely pleased for patients, and survival will improve.”

“The data is amazing ...,” adds Javier Cortes, MD, PhD, head of the Breast Cancer Program of Vall d’Hebron Institute of Oncology in Barcelona, Spain, and also a co-principal investigator of the CLEOPATRA Study Group. “[T]he overall data was absolutely unexpected. … This is the best data we have observed in the history of metastatic breast cancer.”

The Research

Slightly more than 800 study participants were divided into groups, one receiving three drugs — pertuzumab, trastuzumab and docetaxel — and another receiving only trastuzumab and docetaxel.

After the drug infusion, participants were monitored for cardiac safety and progression-free survival, which is the period of time the participants were enrolled in the study without any increase or spread of their cancer.

“Progression-free survival was improved by 6.3 months, and that shows there was a delay in the tumor progressing, and that led to a large increase in overall survival,” Dr. Swain says. “Since the discovery that HER2 would benefit from targeted drugs, pertuzumab plus trastuzumab plus docetaxel, survival has increased dramatically.”

The Drugs

The three-drug combination responsible for enhancing outcomes for study participants included:

  • Pertuzumab: A drug approved by the FDA in 2012, pertuzumab is a recombinant humanized monoclonal antibody that blocks HER2 proteins.
  • Trastuzumab: Also a monoclonal antibody, the drug attaches to the HER2-positive cancer cells and eliminates them or causes them to grow more slowly.
  • Docetaxel: As a taxane drug, it targets cancer cells and prevents them from dividing, which ultimately kills them.

“In the early days when we were working on the trial, it was hard to recruit patients because they weren’t excited about the drugs,” recalls Dr. Swain, noting that other studies at the time seemed more promising and attracted more participants. That was no longer an issue after the initial results of the CLEOPATRA study.

“When I first saw the data, the progression-free survival data, I was shocked that it was so great,” she says. “Now, when I present the final survival analysis, I am still surprised.”

Evolving Treatment Protocols

According to the American Cancer Society, 12 percent of women in the United States will have breast cancer during their lifespan, and more than 230,000 new cases of invasive breast cancer will be diagnosed in 2015. Results from the CLEOPATRA Study Group are altering treatment protocols for patients with HER2-positive breast cancer, researchers note.

“What is clear here is that HER2-based therapy is a standard of care,” Dr. Cortes says. “When we are dealing with metastatic breast cancer, today, I think trastuzumab, pertuzumab and docetaxel chemotherapy should be the first line of defense for these patients.”

“My colleagues have treated a lot of [breast cancer] patients, and with what they have done with the [FDA] approval, ... we have seen remarkable responses and patients not having a relapse,” Dr. Swain says. “The hope is we can use it earlier on and actually cure patients.”

Research Implications

With the CLEOPATRA study as an exemplar, research efforts into treating HER2-positive metastatic breast cancer with targeted drug therapies create the prospect for additional improvements in outcomes. Dr. Swain believes that more research with drug regimens as well as tumor studies will result in further advancements and clinical applications.

“One of the biggest areas of research now is looking at those patients with triple negative breast cancer,” she says. “There is [also] research doing much more analysis of the tumor itself to see what makes it grow.”

“There are many trials … of exciting upcoming drugs,” Dr. Cortes adds. “With this much improvement [in] survival, this is very unusual. … I don’t know if we will see something like this again, but I hope to see it.”